Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study.

Among 365 Hertfordshire Cohort Study participants (aged 59-71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. INTRODUCTION: The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK. METHODS: Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1ß, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors. RESULTS: The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses. CONCLUSIONS: In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the lumbar spine. This adds weight to the theory that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.

Cardiorespiratory fitness not sedentary time or physical activity is associated with cardiometabolic risk in active older adults.

Sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) are associated with cardiometabolic health. Cardiorespiratory fitness (CRF) is also implicated but often overlooked in health recommendations. This study assessed the relationships between ST, MVPA, CRF, and cardiometabolic health in highly active older individuals. 125 healthy amateur cyclists aged 55 to 79 years had their ST and MVPA levels assessed by actigraphy over a 7-day period. CRF was assessed using a maximal effort cycle ergometry test to determine VO2max with results normalized to both body mass and fat-free mass measured by DXA. Markers of cardiometabolic risk (blood glucose, triglycerides, cholesterol, HDL, LDL, Insulin, HOMA IR, blood pressure, and body fat) were assessed and used to determine cumulative cardiometabolic risk. Multiple linear regression was used to assess ST, MVPA, and CRF associations with cardiometabolic health with the relationship between activity levels and CRF determined. CRF was associated with training volume (P = .003), but not ST or MVPA. A high CRF was associated with lower cumulative cardiometabolic risk, body fat percentage, triglyceride, and HDL levels (P < .05 in all cases). MVPA was negatively associated with body fat percentage, while ST was not associated with any marker of cardiometabolic risk when adjusting for activity levels. An association between CRF and cardiometabolic risk even in a group of older individuals with high fitness levels highlights the importance that CRF may have in maintaining health.

Relationships Between Markers of Inflammation and Muscle Mass, Strength and Function: Findings from the Hertfordshire Cohort Study.

We investigated the longitudinal relationships between inflammation markers and the following outcomes in a UK cohort study: appendicular lean mass (ALM); walking speed; level and change in grip strength; and sarcopenia defined by the European Working Group on Sarcopenia in Older People. Analyses were based on 336 community-dwelling older men and women (aged 59-70 years) who participated in the Hertfordshire Cohort Study (HCS). Inflammation markers were ascertained at baseline using enzyme-linked immunosorbent assay techniques and Bio-Plex Pro Assays. Grip strength was measured at baseline and follow-up [median follow-up time: 10.8 years (inter-quartile range 10.2-11.6)] and change in grip strength was ascertained using a residual change approach. At follow-up, ALM was ascertained using dual-energy X-ray absorptiometry, customary walking speed was measured and sarcopenia status was ascertained. Gender-adjusted linear and Poisson regression was used to examine the associations between inflammation markers and outcomes with and without adjustment for anthropometric and lifestyle factors. Higher C-reactive protein was associated (p < 0.04) with lower grip strength and accelerated decline in grip strength from baseline to follow-up. Higher cortisol was associated with lower ALM (p < 0.05). Higher interleukin-8 (IL-8) was associated with lower ALM (p < 0.05) and increased risk of sarcopenia [fully-adjusted relative risk per SD increase in IL-8: 1.37 (95% CI 1.10, 1.71), p = 0.005]. All associations were robust in fully-adjusted analyses. Inflammation markers were associated with measures of muscle mass, strength and function in HCS. Further work is required to replicate these associations and to delineate the underlying mechanisms.

Case of sparganosis: a diagnostic dilemma.

Sparganosis, also known as larval diphyllobothriasis, is a rare disease of humans as man is not a natural host in the life cycle of Spirometra spp. Diagnosis of the latter is difficult as it mimics other conditions that commonly cause subcutaneous or visceral fluid collection. Clinical diagnosis of this particular case was also erroneously labelled as tuberculosis but later labelled as a case of sparganosis. To the best of our knowledge, this is the first case from India where a sparganum-like parasite was isolated in drain fluid from the perinephric area.

Spontaneous intracranial hypotension: case series of rare clinical presentations.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is an increasingly described entity, with over 70 cases reported in the literature. The classic triad includes orthostatic headache, diffuse pachymeningeal enhancement on magnetic resonance imaging (MRI) with gadolinium, and low cerebrospinal fluid pressure (CSF) in the lateral decubitus (< 60 mm H2O) and sitting positions. METHOD: We present four rare clinical presentations of SIH, two of which have not been previously described in the literature, to the best of our knowledge. RESULTS: Patient 1 presented with dyspnea, dysphagia, bilateral ptosis, diplopia and seizures. Patient 2 presented with a paradoxical positional pattern of orthostatic hypotension. In Patient 3, bilateral subdural hematomas (SDH) were encountered; while in Patient 4, a recurrent unilateral SDH requiring multiple surgical interventions was demonstrated. CONCLUSION: Although uncommon clinical presentations, all four cases of intracranial hypotension were spontaneous, demonstrated diagnostic MRI findings, and responded favorably to blood patches or saline injections.

Brain reorganization in patients with spinal cord compression evaluated using fMRI.

OBJECTIVE: This prospective study characterizes the reorganization that occurs within the primary sensorimotor cortices following decompression of cervical spinal stenosis. METHODS: Twelve right-handed patients with cervical myelopathy underwent blood oxygenation level dependent functional MRI (fMRI) prior to decompression and 6 months following surgery. Ten right-handed controls also underwent fMRI. All subjects performed a finger-tapping paradigm with the right hand. Volume time course data were corrected for temporal serial correlation and % normalized before inclusion in the general linear model. Activation maps were created for each group using a threshold of p < 0.005 with Bonferroni correction. Between-group differences in left hemisphere volume of activation (VOA) were measured along the precentral gyrus (PrCG) and postcentral gyrus (PoCG). Each subject also completed clinical questionnaires. RESULTS: Prior to surgery, patients demonstrated a larger VOA (1.23 cm(3), t(max) = 11.8) in comparison to controls within the PrCG. This difference increased following surgery (2.99 cm(3), t(max) = 13.6). Within the PoCG, controls demonstrated a larger VOA (0.53 cm(3), t(max) = 8.28) than preoperative patients. This difference decreased by 0.12 cm(3) (t(max) = 7.05) following surgery. Preoperatively, patients had a 21.7 cm(3) VOA (t(max) = 29.4) within the sensorimotor cortex with the center of gravity located within Brodmann area (BA) 3. Following surgery, the VOA increased to 23.1 cm(3) (t(max) = 26.1) within BA 3. There were significant improvements in clinical outcomes following surgery. CONCLUSIONS: Spinal cord compression resulted in an increase in volume of activation (VOA) within the precentral gyrus (PrCG) and a loss of VOA within the postcentral gyrus (PoCG) in comparison to controls. Surgical decompression results in cortical reorganization with enlarging VOA within both the PrCG and PoCG.

Female genital TB and HIV co-infection.

HIV-induced immunosuppression paves the way for several infections, tuberculosis being very common in our country. Female genital tuberculosis (FGTB), presenting as menstrual irregularities, is a diagnostic challenge in an adolescent female when these may be considered normal. The present case is of a young female who presented with menstrual irregularities, diagnosed subsequently as a case of genital tuberculosis. Microbiological relapse after anti-tubercular treatment of six months caused suspicion of a co-existing immunodeficiency and investigations revealed HIV co-infection; thus emphasizing the need of HIV testing in all patients of tuberculosis for timely diagnosis and treatment support thereafter.

Dysembryoplastic neuroepithelial tumours: clinical, proliferative and apoptotic features.

AIMS: Dysembryoplastic neuroepithelial tumours (DNTs) have been considered benign lesions characterised by a chronic, indolent clinical course. Previous studies have suggested that increased proliferation rates may be balanced by corresponding rates of apoptosis. The objective of this study was to determine whether a correlation exists between histological features and indices of proliferation/apoptosis. METHODS: Fourteen consecutive surgical specimens meeting the histological criteria for DNT were retrospectively reviewed for evidence of aggressive histological features, including anaplasia, mitotic activity, and Ki67 labelling. Immunohistochemistry was performed semiquantitatively to evaluate and compare proliferation (Ki76) and apoptosis (TUNEL). The clinical course of the patients was also reviewed. RESULTS: Atypical histological features were demonstrated in the glial component of select complex DNTs. TUNEL indices, however, had negligible correlation with proliferative indices. A balance between cell proliferation and apoptosis was not evident particularly in those cases displaying aggressive histological features. CONCLUSIONS: While there is no clearly defined clinical or pathological pattern to indicate aggressive growth of DNTs, elevated proliferative indices coupled with atypical histological features in complex DNTs should be taken into consideration in determining the aggressiveness of surgical extirpation and follow-up until experience with these uncommon tumours is greater.

Recent outbreak of meningococcal meningitis--a microbiological study with brief review of literature.

Meningococcal disease presents in various clinical forms, most common being meningitis and meningococcemia. A spurt of meningococcal cases was seen in medicine and pediatric wards of Dr. Ram Manohar Lohia Hospital during the recent outbreak from Dec 2005 - June 2006. These had presented either with the classical features of acute purulent meningitis or as fever with rash. The patients were investigated microbiologically for the causative organism which was identified as Neisseria meningitidis in 257 out of 531 cases (48.39%). The classic finding of gram negative diplococci on gram stain remained the mainstay of diagnosis. N. meningitidis isolates from culture were sensitive to all commonly used antibiotics.

Spontaneous chronic spinal subdural hematoma associated with spinal arachnoiditis and syringomyelia.

Spontaneous chronic spinal subdural hematoma is rare. We describe a case of spontaneous chronic spinal subdural hematoma associated with arachnoiditis and syringomyelia in a 76-year old woman who presented with a 14-year history of progressive myelopathy. MRI scan revealed a thoraco-lumbar subdural cystic lesion and a thoracic syrinx. The patient underwent thoracic laminectomy and decompression of the lesion, which was a subdural hematoma. A myelotomy was performed to drain the syrinx. Pathological examination revealed features consistent with chronic subdural membrane. This report attempts to elucidate the pathogenesis of chronic spinal subdural hematoma. We discuss possible etiological factors in light of the current literature and pathogenesis of both spinal subdural hematoma and syrinx formation.

MAP2 and nestin co-expression in dysembryoplastic neuroepithelial tumors.

BACKGROUND: The ontogeny and maturity of neurons and oligodendroglia-like cells (OLC) found in dysembryoplastic neuroepithelial tumors (DNT) remains controversial. A developmental origin has been proposed based on the close association to cortical dysplasia and the benign microscopic and clinical course. Our goal was to characterize the expression of nestin, a neuroepithelial precursor/stem cell antigen in DNT, along with other pathological and clinical features of this entity. METHODS: The clinical and operative features of 13 surgical specimens meeting the histological criteria for DNT were reviewed. Nestin, microtubule-associated protein 2 (MAP2), neurofilament (NF) and glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry and confocal scanning laser microscopy. RESULTS: Select neuronal cells in all cases demonstrated strong MAP2 immunoreactivity. Nestin-positive cells of neuronal morphology were found in 6 cases. OLC demonstrated frequent selective staining for MAP2, GFAP and nestin. Confocal microscopy demonstrated numerous examples of cells co-expressing nestin and MAP2. CONCLUSIONS: Our study suggests that OLCs represent a united population of immature neuronal (nestin + MAP2) and glial (GFAP) phenotypes. Larger, morphologically recognizable neurons also showed occasional co-expression of nestin and MAP2, suggesting a degree of dysmaturity in common with their OLC counterparts. The apparent mixed lineage of OLCs lends support to theories suggesting that DNTs arise from pluripotent neuroepithelial cells.

Selective vulnerability of the lumbosacral spinal cord after cardiac arrest and hypotension.

BACKGROUND AND PURPOSE: It is generally accepted that the gray matter in the watershed area of the midthoracic level of the spinal cord is the ischemic watershed zone of the spinal cord. We performed a retrospective study to reevaluate the frequency and distribution of spinal cord injury after a global ischemic event. METHODS: Clinical files and neuropathology specimens of all adult patients with either a well-documented cardiac arrest or a severe hypotensive episode, as well as pathologically confirmed ischemic encephalopathy and/or myelopathy, were reviewed by an independent reviewer. RESULTS: Among 145 cases satisfying selection criteria, ischemic myelopathy was found in 46% of patients dying after either a cardiac arrest or a severe hypotensive episode. Among the patients with myelopathy, predominant involvement of the lumbosacral level with relative sparing of thoracic levels was observed in >95% of cardiac arrest and hypotensive patients. None of the examined patients developed neuronal necrosis limited to the thoracic level only. CONCLUSIONS: Our findings indicate a greater vulnerability of neurons in the lumbar or lumbosacral spinal cord to ischemia than other levels of the spinal cord.

Nestin expression in cortical dysplasia.

OBJECT: It is recognized that cortical dysplasia (CD) is associated with an increased incidence of glioneuronal neoplasms. Among hypothetical considerations, there is the possibility that CD and other neuronal migration abnormalities harbor dysmature cells with the potential to give rise to glioneuronal neoplasms. Such cells, if present, would be reasonably expected to display immature features. The goal of the present study was to characterize the expression of nestin, a neuroepithelial precursor/stem cell antigen, in CD, along with other pathological and clinical features of this entity. METHODS: Clinical and surgical features of 10 recent cases meeting the histological criteria for CD were reviewed. Expressions of nestin, MAP2, neurofilament, and glial fibrillary acidic protein (GFAP) were assessed using immunohistochemical analysis and confocal scanning laser microscopy. Immunoreactivity for both glial and neuronal antigens as well as nestin was found in a select group of cells within regions of CD. Immunohistochemical and confocal microscopic findings demonstrated that these cells with neuronal or ambiguous features are a mixed population, some of which are dysmature neurons (positive for nestin and MAP2), whereas others are astrocytic (positive for nestin and GFAP). CONCLUSIONS: Further insight into the nature of nestin-positive neurons may shed light on the cause and pathogenesis of the associated glioneuronal tumors and the accompanying chronic seizures.

Malignant transformation of a dysembryoplastic neuroepithelial tumor. Case report.

A 29-year-old man presented in 1984 with a recent onset of partial seizures marked by speech arrest. Electroencephalography identified a left frontotemporal dysrhythmia. Computerized tomography (CT) scanning revealed a superficial hypodense nonenhancing lesion in the midleft frontal convexity, with some remodeling of the overlying skull. The patient was transferred to the London Health Sciences Centre for subtotal resection of what was diagnosed as a "fibrillary astrocytoma (microcystic)." He received no chemotherapy or radiation therapy and remained well for 11 years. The patient presented again in late 1995 with progressive seizure activity. Both CT and magnetic resonance imaging demonstrated a recurrent enhancing partly cystic lesion. A Grade IV astrocytoma was resected, and within the malignant tumor was a superficial area reminiscent of a dysembryoplastic neuroepithelial tumor (DNT). Data on the lesion that had been resected in 1984 were reviewed, and in retrospect the lesion was identified as a DNT of the complex form. It was bordered by cortical dysplasia and contained glial nodules, in addition to the specific glioneuronal element. The glial nodules were significant for moderate pleomorphism and rare mitotic figures. The Ki67 labeling index averaged 0.3% in the glial nodules and up to 4% focally. Cells were rarely Ki67 positive within the glioneuronal component. This case is the first documented example of malignant transformation of a DNT. It serves as a warning of the potential for malignant transformation in this entity, which has been traditionally accepted as benign. This warning may be especially warranted when confronted with complex forms of DNT. The completeness of resection in the benign state is of paramount importance.

Case of the month: April 1998--30 year old male with perineal numbness.

A 30-year-old male presented with a 2 year progressive course of bowel and bladder dysfunction, mild leg weakness and sensory abnormalities in sacral dermatomes. MRI showed an intra-axial conus medullaris lesion which was excised and identified as a ganglioglioma. The case presents the typical clinical course and histopathology of this unusual lesion which carries a favorable prognosis after gross total removal. Preoperative neurological function in such patients is highly predictive of post-operative outcome.

Nestin expression in reactive astrocytes following focal cerebral ischemia in rats.

During central nervous system (CNS) development, intermediate filaments are subjected to a sequential remodelling process. Nestin is a distinct intermediate filament which is transiently expressed in proliferating neuroepithelial stem cells during the neurulation stage of development. Nestin re-expression in the adult rat was studied following transient (2 h) middle cerebral artery occlusion. Seven days after the ischemic insult, nestin reactive astrocytes were found in the border zone surrounding cerebral infarction. Nestin immunoreactivity delineated a zone between infarction and the surrounding intact cerebral parenchyma. In situ hybridization for nestin mRNA showed early changes in small cells in the surround of the ischemic lesion. These results with nestin, along with other stem cell markers expressed by reactive astrocytes, suggest an embryonic reversion of the mature cytoskeleton as a response of astrocytes to cerebral injury.

Association of pleomorphic xanthoastrocytoma with cortical dysplasia and neuronal tumors. A report of three cases.

BACKGROUND: Several recent publications indicate that pleomorphic xanthoastrocytoma (PXA) may occasionally express ganglionic cell differentiation, linking this type of tumor to other benign, mixed glioneuronal neoplasms. Furthermore, ganglionic tumors and less frequently some benign glial tumors in the central nervous system, could be associated with a variety of mild developmental abnormalities of the cerebral cortex that are classified under the broad term cortical dysplasia. The association of cortical dysplasia with PXA and a neuronal pattern of differentiation has not been reported previously. METHODS: The authors present clinical, radiologic, immunohistochemical, and ultrastructural findings in three patients with cortical dysplasia. The cortical dysplasia was continuous with PXA, displaying an additional component of neuronal cell differentiation. RESULTS: The ages of the patients were 23, 47, and 52 years. Resection of the tumors was predated by temporal lobe seizures by 6 years in 1 patient and by more than 30 years in the others. In all 3 cases, radiologic studies conducted 3-6 years before surgery showed either no abnormality or lesions that were initially nonprogressing. CONCLUSIONS: The longstanding clinical history of seizures and the existence of radiologically documented dormant lesions several years before tumor removal both suggest that PXA in these patients very likely developed in benign hamartomatous cortical lesions or in preexisting cortical dysplasia. The authors' findings, along with the consistent occurrence of PXA in the gray matter in the majority of the reported cases, indicate that these tumors may originate either from a subclass of astrocytes histogenetically and topographically associated with neurons or from multipotential neuroectodermal precursor cells common to neurons and astrocytes.

Cellular radiosensitivity and DNA damage in primary human fibroblasts.

PURPOSE: To evaluate the relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts to decide whether the initial or residual DNA damage levels are the more predictive of normal tissue cellular radiosensitivity. METHODS AND MATERIALS: Five primary human nonsyndromic and two primary ataxia telangiectasia fibroblast strains grown in monolayer were studied. Cell survival was assessed by clonogenic assay. Irradiation was given at high dose rate (HDR) 1-2 Gy/min. DNA damage was measured in stationary phase cells and expressed as fraction released from the well by pulsed-field gel electrophoresis (PFGE). For initial damage, cells were embedded in agarose and irradiated at HDR on ice. Residual DNA damage was measured in monolayer by allowing a 4-h repair period after HDR irradiation. RESULTS: Following HDR irradiation, cell survival varied between SF2 0.025 to 0.23. Measurement of initial DNA damage demonstrated linear induction up to 30 Gy, with small differences in the slope of the dose-response curve between strains. No correlation between cell survival and initial damage was found. Residual damage increased linearly up to 80 Gy with a variation in slope by a factor of 3.2. Cell survival correlated with the slope of the dose-response curves for residual damage of the different strains (p = 0.003). CONCLUSION: The relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts of differing radiosensitivity is closest with the amount of DNA damage remaining after repair. If assays of DNA damage are to be used as predictors of normal tissue response to radiation, residual DNA damage provides the most likely correlation with cell survival.

Tubercular mastitis.

Tuberculosis, a relatively rare lesion in the breast, was observed in 18 patients (seventeen of whom were of child bearing age) with an incidence of 1.02%. Coincidental tuberculosis of the faucial tonsils of suckling infants is suggested as the most common route of infection, especially in the primary type of tubercular mastitis. Conservative surgery under antitubercular therapy cover was found most appropriate.